(-)Deprenyl is a selective inhibitor of monoamine oxidse (MAO) type B. MAO-B uses a preferential substrates phenylethylamine and dopamine, while MAO-A preferentially catabolizes norepinephrine (NE), dopamine and serotonin (5HT). At a dose of 5 mg per day, which selectively inhibits the MAO-B, (-)deprenyl relieved many symptoms of depressed patients without eliciting the strong side-effects induced by other MAO inhibitors. In rats receiving (-)deprenyl (1 Mumol/kg, s.c., for 21 days) the NE-stimulated cAMP accumulation and the Beta-adrenergic receptor number in minces and crude synaptic membranes from frontal cortex were significantly decreased. Moreover after the same treatment schedule the number of 3H-imipramine recognition sites in frontal cortex and hippocampus was significantly increased. Interestingly, (-)deprenyl is not active "in vitro" as a displacer of 3H-imipramine specifically bound to rat brain membranes, and the possibility that this effect is due to the formation of one of the (-)deprenyl metabolites, amphetamine, or to the blockade of MAO-B, was ruled out. A selective lesion of the 5HT axon terminals prevented the increase of 3H-imipramine binding and the attenuation of the Beta-adrenergic-coupled cAMP generating system evinced by repeated injections of (-)deprenyl. These results suggest that many of the (-)deprenyl are typical of the antidepressant actions and that a primary modification of the serotonergic neurons can determine the attenuation of signal amplification at noradrenergic receptors, believed to mediate the relief of symptoms of affective disorders.